Key result
SID-1 proteins act as dsRNA receptors in endocytosis rather than direct channels.
Why the study?
The dsRNA uptake mechanism by SID-1 family proteins is largely unknown despite their roles in RNA transport and immune functions.
This review summarizes recent structural studies to provide insights into the double-stranded RNA transport mechanism of SID-1 family proteins.
Challenges channel model of SID-1; leaves open receptor-targeted RNAi delivery strategies pending mammalian validation.
The systemic RNA interference defective 1 (SID-1) family proteins are putative double-stranded RNA (dsRNA) transporters. Two mammalian homologs, SIDT1 and SIDT2 have been linked to many functions such as innate immune responses, microRNA uptake and lysosomal degradation of RNA/DNA whereas Caenorhabditis elegans SID-1 is essential for systemic RNA interference. However, dsRNA uptake mechanism is largely unknown. In this review, we discuss our current understanding of the molecular functions of SID-1 family proteins at a structure level, which highlights recent structural studies.
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Hirano et al. (2024) reported a review. Structural studies of SID-1 family proteins reveal they lack tunnels for dsRNA pass-through, suggesting they function as dsRNA receptors in endocytosis rather than direct channels.
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